OBJECTIVES: 1. Study the role of ligandin and Z protein in the transfer of various organic anions from plasma into the liver, and in their subsequent intracellular fate. 2. Define the structural basis for anion binding by ligandin, subunit structure and heterogeneity, nature of the binding site, and binding properties of ligandin in the environment of the liver cell. 3. Purification of fractions rich in plasma membrane facing the hepatic sinusoid, bile canaliculi and lateral portion of the cell; study the specificity, site and nature of binding of bilirubin, bilirubin conjugates and other organic anions, and examination of these parameters in pathologic conditions. 4. Characterization of the enzyme ("transglucuronidase") which converts bilirubin monoglucuronide to bilirubin glucuronide: study its mechanism, localization, and regulation, relationship to the transfer of diglucuronides from liver into bile, and possible role in various inheritable and acquired hepatobiliary diseases. 5. Continue to characterize the primary functional defect, pathogenesis, and mode of transmission of various types of inheritable jaundice in man and animals. 6. The diagnostic and prognostic value of serum and urinary ligandin measurements in hepatobiliary and renal diseases.